The aim of this research is to better define the interaction of acetylcholinesterase and nerve membranes. The possible orientation of this enzyme with respect to the membrane surface will be studied. In addition, changes in orientation and/or conformation upon chemical or electrical perturbation (stimulation) of the membrane will be studied. Direct physical data relevant to the geometrical orientation of membrane associated proteins is sparse in general, and non- existant for acetylcholinesterase. The techniques of spin-labeling combined with EPR, NMR and flourescence spectroscopy will be used. Spin-label and flourescent probes will be used to explore both the enzyme and lipid contributions to the enzyme-membrane interaction. These studies will increase our understanding of the molecular mechanism by which nerves function.